In this project we will develop new biomarkers and algorithms for use in epidemiological studies of women's reproductive health. Methods will be developed for assessing pituitary function and early fetal loss by the identification of different molecular forms of the secreted pituitary and trophoblastic gonadotropins. Practical assays will be developed for detecting the corresponding metabolites that are excreted in urine samples. Algorithms for assessing abnormalities of menstrual function in epidemiological field studies will be developed to utilize the biomarker data which can be generated with existing urinary assays. These algorithms will be utilized for identification of the effects of environmental exposure on the pre-ovulatory and peri-ovulatory phases of the menstrual cycle, when perturbations of the ovarian function may lead to decreased fertility. Trophoblastic function will be characterized in studies of the ovarian response to healthy and failing embryos. The pattern of ovarian response will be studied in relation to the normalcy of trophoblastic support in the peri-implantation period. Clinical research studies will provide basic information for identification of new biomarkers, for validation of assay methods, and for testing algorithms. All new tests will be applied to urine samples which have been collected and analyzed in previous epidemiological and toxicologic studies.